title: Structural and functional relationships of natural and artificial dimeric bovine ribonucleases: new scaffolds for potential antitumor drugs.
abstract: Protein aggregation via 3D domain swapping is a complex mechanism which can lead to the acquisition of new biological, benign or also malignant functions, such as amyloid deposits. In this context, RNase A represents a fascinating model system, since by dislocating different polypeptide chain regions, it forms many diverse oligomers. No other protein displays such a large number of different quaternary structures. Here we report a comparative structural analysis between natural and artificial RNase A dimers and bovine seminal ribonuclease, a natively dimeric RNase with antitumor activity, with the aim to design RNase A derivatives with improved pharmacological potential.
authors.affiliation: Dipartimento di Scienze della Vita e della Riproduzione, Sezione di Chimica Biologica, Università degli Studi di Verona, Strada Le Grazie 8, I-37134 Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gotte
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Laurents
authors.forename: Antonello
authors.initials: A
authors.lastname: Merlino
authors.forename: Delia
authors.initials: D
authors.lastname: Picone
authors.forename: Roberta
authors.initials: R
authors.lastname: Spadaccini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D020134:Catalytic Domain; D015195:Drug Design; D004722:Endoribonucleases / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D012259:Ribonuclease, Pancreatic / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004722:Endoribonucleases; C032523:ribonuclease SPL; D012259:Ribonuclease, Pancreatic
keywords: 3D-domain swapping; Antitumor RNase; Bovine seminal ribonuclease; Dimeric RNase; Protein aggregation; Ribonuclease A